tbuckley/cabot-search huggingface dataset:
Survival in patients with breast cancer and history of autoimmune disease.
Authors: Demitrios Dedousis, Annie Zhang, Anastasia Vassiliou, Shufen Cao, Deepthi Yammani, Ravi Kumar Kyasaram, John Shanahan, Melissa C. Keinath, Melinda Laine Hsu, Pingfu Fu, Afshin Dowlati, Alberto J. Montero
Journal: Journal of Clinical Oncology (2022)

1020 Background: Patients with autoimmune disease, specifically systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjogren syndrome, are at reduced risk of developing breast cancer compared to those without a prior history of autoimmune disease. Despite this, little is known about the survival of patients with concurrent autoimmune disease and breast cancer. This study compared outcomes in patients with breast cancer with and without autoimmune disease. Methods: This study was a retrospective analysis of patients from SEER-Medicare databases from 2007-2014 with breast cancer. Patients with a history of autoimmune disease were identified using ICD-9 codes. The effects of autoimmune disease on overall survival (OS) and cancer-specific survival (CSS) were estimated using multivariable Cox regression and Gray’s method respectively controlling the effects of age, race and chronic kidney disease (CKD). The cumulative CSS was estimated taking death as a competing risk. Results: The overall prevalence of investigated autoimmune diseases among the 137,324 patients with breast cancer was 26.69%. The most common autoimmune diseases identified were RA (23.35%), psoriasis (2.41%) and SLE (1.12%). In stage IV breast cancer patients the OS and CSS were significantly higher in patients with autoimmune disease (p values &lt; 0.0001), with a median OS of 36 months compared to 30 months in patients without autoimmune disease. After adjusting for the effects of age, race, and CKD, autoimmune disease was still predictive of higher OS (HR: 1.46, 95% CI: 1.37 – 1.57, p &lt; 0.0001) and CSS (HR: 1.39, 95% CI: 1.29 – 1.5, p &lt; 0.0001). Patients with autoimmune disease and stage I-III breast cancer, had lower OS (p &lt; 0.0001, p &lt; 0.0001, and p = 0.026 respectively) compared to patients without autoimmune disease. Conclusions: We found a higher prevalence of RA, Crohn disease, ulcerative colitis, and SLE in patients with breast cancer compared to cohorts of similar age ranges in the general population. History of autoimmune disease resulted in significantly improved OS and CSS in patients with stage IV breast cancer even when controlling for age, race and CKD, in this pre-immunotherapy cohort. These results suggest that that anti-tumor immunity plays an important role in late-stage breast cancer, and could be potentially exploited to improve the effectiveness of immunotherapy. Further research into the relationship between autoimmunity and breast cancer is warranted.
Symptom profiles and health care utilization in long-term survivors of Survivors of Childhood Childhood Cancer Survivor (CCSS) study.
Authors: Rachel Tillery Webster, Wei Liu, Meghan Eileen McGrady, Nicole M. Alberts, Tara M. Brinkman, Kirsten K. Ness, Bernard Fuemmeler, Alicia Kunin-Batson, Deokumar Srivastava, I-Chan Huang, Gregory T. Armstrong, Rebecca M. Howell, Daniel M. Green, Yutaka Yasui, Kevin R. Krull
Journal: Journal of Clinical Oncology (2022)

e22024 Background: Physical and psychological symptoms co-occur among survivors of childhood cancer, and subgroups with high symptom burden may be at increased risk for problematic healthcare utilization (HCU). Methods: Childhood Cancer Survivor Study participants (N = 17,231; Mean [SD] age = 27.4 [5.98]; 79% non-Hispanic White; 48% female) self-reported sensory, motor, cardiac, respiratory, pain, gastrointestinal, fatigue, memory, depression, and anxiety symptoms at baseline evaluation and latent class analysis identified symptom profiles. Chronic health conditions (CHCs) at baseline (graded per CTCAE 1-2 [mild or moderate; reference] vs 3-4 [severe-life threatening or disabling). HCU (no health care, general care, oncology-focused, long-term follow-up, emergency room visit) for the past 2 years was assessed 6.3 median years after baseline. Logistic regressions examined associations between class membership and follow-up HCU, adjusted for sex, age, health insurance and CHCs. Results: Five symptom classes were identified: 1) Global symptoms (global; 7.7%); 2) emotional distress and pain (distress-pain; 13.3%); 3) neurologic and pain (neuro-pain; 10.6%); 4) cardiopulmonary and pain (cardio-pain; 5.3%); 5) non-elevated symptoms (norm; 63.1%). Bone tumor survivors had higher risk of falling into global, neuro-pain and cardio-pain groups (p’s &lt; .001), and CNS tumor survivors had higher risk of falling into global and neuro-pain group (all p &lt; .001) compared to leukemia survivors. Radiation, Grade 3-4 CHCs, female sex, and older age increased risk of global, distress-pain, neuro-pain and cardio-pain membership compared to norm (all p’s &lt; .001). Oncology-focused care was more common in cardio-pain and global symptom groups, while long-term follow-up care was more common in neuro-pain and global groups (Table). All elevated symptoms groups were more likely to have emergency room visits compared to norm group. Conclusions: Adjusting for insurance, CHCs and older age, elevated symptoms are associated with future emergency room use. Pain is prevalent in all high symptom groups, and suggests an important intervention target.[Table: see text]
Subcutaneous daratumumab (DARA SC) versus active monitoring in patients (pts) with high-risk smoldering multiple myeloma (SMM): Randomized, open-label, phase 3 AQUILA study.
Authors: Meletios A. Dimopoulos, Peter M. Voorhees, Hartmut Goldschmidt, Ross I. Baker, Yingqi Shi, Els Rousseau, Robyn Monet Dennis, Robin L. Carson, S. Vincent Rajkumar
Journal: Journal of Clinical Oncology (2022)

TPS8075 Background: Standard of care for SMM includes active monitoring until progression to multiple myeloma (MM); however, recent evidence suggests pts with high-risk features may benefit from early treatment. DARA is a human IgGκ monoclonal antibody targeting CD38 that is approved as monotherapy for relapsed/refractory MM (RRMM) or in combination with standard of care for RRMM or newly diagnosed MM. Results from the phase 3 COLUMBA study showed that DARA SC demonstrated similar efficacy to intravenous (IV) DARA but with a lower rate of infusion-related reactions and shorter administration time. Based on the promising single-agent activity observed with IV DARA in intermediate- or high-risk SMM pts during the phase 2 CENTAURUS study, we hypothesized that DARA SC may delay progression to MM versus active monitoring in pts with high-risk SMM. Methods: AQUILA is an ongoing, randomized, open-label, multicenter phase 3 study of DARA SC versus active monitoring in pts with high-risk SMM. DARA SC (DARA 1,800 mg + recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; Halozyme]) is administered by manual injection over approximately 5 minutes at alternating locations on the abdomen weekly in Cycles 1 and 2, every 2 weeks in Cycles 3-6, and every 4 weeks thereafter until 39 cycles (28 days/cycle), up to 36 months, or until disease progression. Eligibility criteria include confirmed diagnosis of SMM for ≤5 years, factors indicating high risk of progression to MM (clonal bone marrow plasma cells [BMPCs] ≥10% and ≥1 of the following: serum M protein ≥30 g/L, IgA SMM, immunoparesis with reduction of 2 uninvolved Ig isotypes, serum involved:uninvolved free light chain ratio ≥8 to &lt; 100, or clonal BMPCs &gt; 50% to &lt; 60% with measurable disease), and ECOG performance status ≤1. The primary endpoint is progression-free survival (PFS), assessed by an independent review committee, with disease progression defined according to International Myeloma Working Group diagnostic criteria for MM. Secondary endpoints include time to biochemical or diagnostic (SLiM-CRAB) progression, overall response rate, complete response rate, duration of response, time to response, time to first-line treatment for MM, PFS on first-line treatment for MM (PFS2), overall survival, and incidence of MM with adverse prognostic features. The study completed enrollment on May 6, 2019; 390 pts have been randomly assigned to DARA SC or active monitoring. The primary efficacy analysis will be performed after approximately 165 PFS events have been observed. Clinical trial information: NCT03301220.
Efficacy and safety of dacomitinib in advanced non-small cell lung cancer patients harboring uncommon <i>EGFR</i> mutations: Real-world evidence from China.
Authors: Hong-Shuai Li, Guangjian Yang, Yi Cai, Junling Li, Haiyan Xu, Tao Zhang, Liqiang Zhou, Jiancheng Luo, Yuying Wang, Jinliang Wang, Xingsheng Hu, Peng Liu, Xiang Yan, Yan Wang
Journal: Journal of Clinical Oncology (2022)

e21163 Background: Dacomitinib has been approved for advanced non-small cell lung cancer (NSCLC) patients harboring common epidermal growth factor receptor ( EGFR) alterations; however, clinical evidence on its activity to uncommon EGFR mutations is currently limited. Methods: Patients were collected from the Chinese National Cancer Center and the Chinese PLA hospital between July 2017 and December 2021. The objective response rate and disease control rate were determined by RECIST 1.1. Adverse events were assessed by CTCAE 5.0. Kaplan-Meier method was utilized to assess progression-free survival (PFS). Results: In total, 38 advanced NSCLC patients harboring uncommon EGFR mutations treated with dacomitinib in multi-line settings were enrolled. Among these patients, 30 cases carried major uncommon mutations, of which 13 cases harbored G719A/C, 8 carried S768I + G719A/C/S, 7 had L861Q, 2 had L861Q + G719A, and the remaining 8 patients carried non-major uncommon mutations, of which 3 harbored E709X, 3 carried L747P, 1 had H183D, and 1 had G598V. The initial dose of dacomitinib (45 mg, 30 mg, or 15 mg once daily) was based on the performance status and comorbidities of the patient. In the whole cohort, 55.3 % of patients (21/38) had a confirmed partial response and 89.5 % (34/38) had disease control, and the median PFS was 10.3 months (95 % confidence interval [CI], 5.8–14.8). For non-major uncommon mutations, 62.5 % of patients (5/8) had a confirmed partial response and 87.5 % (7/8) had disease control, and the median PFS was 11.5 months (95 % CI, 6.2–16.8). Except for one case not available for brain evaluation, control of the intracranial metastases was observed in 16 patients (16/18, 88.9 %), and the median PFS was 6.6 months (95 % CI, 6.3–6.9). Subgroup analysis did not show a significant difference in PFS between patients with and without major uncommon mutations (HR = 0.786, 95 % CI 0.265-2.331, P = 0.639), but between those with and without brain metastases (HR = 3.350, 95 % CI 1.334-8.411, P = 0.005). No grade 4-5 adverse events (AEs) occurred, but all patients had grade 1–2 AEs, and 13.2 % (5/38) of patients required a dosage reduction due to intolerable AEs. Conclusions: This real-world study indicates that dacomitinib is potent and well-tolerated in NSCLC patients harboring uncommon EGFR mutations in multi-line settings, and has favourable activity for brain metastases.[Table: see text]
Shifting perceptions of alternative therapies in cancer patients during the COVID-19 pandemic: Results from the Complementary and Alternative Medicine Exposure in Oncology (CAMEO) Study.
Authors: Christopher R. Weil, Ryan J. Hutten, Brandon M. Barney, Angela Fagerlin, David K. Gaffney, David Michael Gill, Gary Whipple, Terence Duane Rhodes, Laura Scherer, Gita Suneja, Jonathan David Tward, Theresa Louise Werner, Skyler B Johnson, Jaden D. Evans
Journal: Journal of Clinical Oncology (2022)

e24130 Background: Complementary and alternative medicine (CAM) use has been associated with worse survival outcomes in cancer patients compared to standard of care therapies. CAM has received a significant increase in public awareness and interest in the COVID-19 pandemic era. We sought to understand how the COVID-19 pandemic affected CAM use and perceptions in cancer patients. Methods: Data was collected from adult cancer patients prospectively enrolled on a cross-sectional survey conducted at an NCI-designated cancer center and a comprehensive cancer center between 2020 and 2021. The survey included questions assessing changes in patient attitude towards CAM and likelihood of using CAM, both relative to prior to COVID-19. Analyzed CAM users included those taking vitamin, mineral and herbal supplements, alternative medicines and special diets, and excluded mind-body practices as the focus of this analysis was on enteral and parenteral CAM therapies. Differences in the impact of COVID-19 on CAM use beliefs and practices between CAM users and non-users were analyzed with χ 2 and two-sample t-tests. Results: Out of 749 respondents, 578 (77%) used any CAM and 470 (63%) used enteral or parenteral CAM. Results shown in table. Compared to prior to COVID-19, CAM users were more likely to view CAM more favorably (12% vs 5%, p &lt; 0.01), while non-users were more likely to have an unchanged opinion (90% vs 84%, p = 0.03). Females had higher rates of viewing CAM more favorably than males (80% vs 58%, p = 0.04). Patients who viewed CAM more favorably had higher rates of self-reported incurable cancer (36% vs 11%, p = 0.04), declining recommended hormone therapy (22% vs 0%, p &lt; 0.01), and higher trust of social media (19% vs 0%, p = 0.02) and websites (24% vs 0%, p &lt; 0.01). Since the start of COVID-19, CAM users were more likely to report increased likelihood of using CAM (12% vs 6%, p = 0.01). Patients who were more likely to use CAM had higher rates of declining recommended chemotherapy (12% vs 0%, p = 0.02), and higher trust of social media (15% vs 2%, p = 0.01) and websites (28% vs 7%, p &lt; 0.01). Conclusions: During the COVID-19 pandemic, attitudes on CAM use in oncology patients have become increasingly polarizing. Patients with favorable attitudes toward CAM were likely to decline recommended standard of care therapy and more like to use CAM since COVID-19. This data helps characterize shifting attitudes toward CAM and may help guide shared decision-making between physician and patient.[Table: see text]
distAngsd: Fast and Accurate Inference of Genetic Distances for Next-Generation Sequencing Data
Authors: Lei Zhao, Rasmus Nielsen, Thorfinn Sand Korneliussen
Journal: Molecular Biology and Evolution (2022)

Abstract Commonly used methods for inferring phylogenies were designed before the emergence of high-throughput sequencing and can generally not accommodate the challenges associated with noisy, diploid sequencing data. In many applications, diploid genomes are still treated as haploid through the use of ambiguity characters; while the uncertainty in genotype calling—arising as a consequence of the sequencing technology—is ignored. In order to address this problem, we describe two new probabilistic approaches for estimating genetic distances: distAngsd-geno and distAngsd-nuc, both implemented in a software suite named distAngsd. These methods are specifically designed for next-generation sequencing data, utilize the full information from the data, and take uncertainty in genotype calling into account. Through extensive simulations, we show that these new methods are markedly more accurate and have more stable statistical behaviors than other currently available methods for estimating genetic distances—even for very low depth data with high error rates.
<i>SimplifyEnrichment</i>: A Bioconductor Package for Clustering and Visualizing Functional Enrichment Results
Authors: Zuguang Gu, Daniel Hübschmann
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Functional enrichment analysis or gene set enrichment analysis is a basic bioinformatics method that evaluates the biological importance of a list of genes of interest. However, it may produce a long list of significant terms with highly redundant information that is difficult to summarize. Current tools to simplify enrichment results by clustering them into groups either still produce redundancy between clusters or do not retain consistent term similarities within clusters. We propose a new method named binary cut for clustering similarity matrices of functional terms. Through comprehensive benchmarks on both simulated and real-world datasets, we demonstrated that binary cut could efficiently cluster functional terms into groups where terms showed consistent similarities within groups and were mutually exclusive between groups. We compared binary cut clustering on the similarity matrices obtained from different similarity measures and found that semantic similarity worked well with binary cut, while similarity matrices based on gene overlap showed less consistent patterns. We implemented the binary cut algorithm in the R package simplifyEnrichment, which additionally provides functionalities for visualizing, summarizing, and comparing the clustering. The simplifyEnrichment package and the documentation are available at https://bioconductor.org/packages/simplifyEnrichment/.
Take charge during treatment: A planned exercise protocol to evaluate disparities and cardiovascular outcomes in Black and White patients with breast cancer undergoing treatment.
Authors: Mary Hidde, Andreas M Beyer, Kirsten M. M. Beyer, Matthew J Durand, Shane A Phillips, Georgios Grigoriadis, Courtney Jankowski, Madeline Berendt, Bethany Canales, Laura Norwood Toro, Amanda L. Kong, Kent Hoskins, Sherry-Ann Brown, David Gutterman, Melinda Stolley
Journal: Journal of Clinical Oncology (2022)

TPS12138 Background : Cardiotoxicity is a significant challenge associated with common first-line breast cancer (BC) chemotherapy (CTx) treatments including anthracyclines (AC) and targeted therapies, such as anti-Her-2 therapy. For targeted therapies, cardiac complications typically resolve once treatment is completed or stopped. For ACs, treatment may lead to permanent long term cardiac damage, and elevated risk for major adverse cardiovascular events (MACE). Black/African American (B/AA) women are at higher risk for AC-based cardiotoxicity compared to Non-Hispanic White (NHW) women. To date, most efforts have targeted managing and defining mechanisms of large vessels and cardiac damage. However, impaired microvascular function, a powerful but clinically underused predictor of future MACE, may also be implicated. Extensive evidence shows that exercise interventions reduce systemic inflammation and possibly MACE. However, few cardio-oncology studies have utilized exercise to mitigate cardiotoxicity, and none have quantified microvascular endothelial function. A further gap in cardio-oncology research is a paucity of studies focused on understanding and addressing disparities. This research project aims to 1) test the feasibility and efficacy of an exercise intervention designed to mitigate the effects of CTx, Take Charge during Treatment (TCT) and 2) examine the influence of socio-ecological factors on endothelial function in response to an exercise intervention. Methods: B/AA (n=50) and NHW (n=50) women diagnosed with non-metastatic BC, scheduled to receive AC and/or anti-HER-2 therapy, will be recruited and randomized to participate in the TCT intervention or usual care (NCT05223322). TCT is a virtual exercise coaching program with weekly coaching sessions, six of which include supervised exercise. Assessments to assess socio-ecologic and vascular outcomes are presented in the Table. Assessments will be completed prior to treatment (T1), after treatment completion (18-24 weeks, T2), and 12-months post treatment (T3). Clinical trial information: NCT05223322. [Table: see text]
Linkage of time interval from neoadjuvant chemoradiotherapy to surgery with pathological response and survival profile in resectable esophageal cancer patients.
Authors: Jiaqi Liu, Xiaoxiao Zeng, Xiaojuan Zhou, Yong Xu, Zhenyu Ding, Yang Hu, Yong Yuan, Longqi Chen, Jin Wang, You Lu, Yongmei Liu
Journal: Journal of Clinical Oncology (2022)

e16071 Background: The optimal time interval from neoadjuvant chemoradiotherapy (nCRT) to surgery remains controversial in esophageal cancer (ESC) patients. Hence, this study aimed to evaluate the relationship of the time interval from nCRT to surgery with the prognosis in ESC patients. Methods: Totally, 166 ESC patients treated with nCRT followed by surgical resection were reviewed. Their pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS) were analyzed. Based on the median duration from nCRT to surgery, patients were classified into duration from nCRT to surgery ≥66 days group or &lt;66 days group. Results: The pCR rate was elevated in duration from nCRT to surgery ≥66 days group compared to &lt;66 days group (48.3% vs. 25.3%, P = 0.002), while DFS ( P = 0.316) and OS ( P = 0.883) were of no difference between these two groups. The duration from nCRT to surgery (≥66 days vs. &lt;66 days) (odds ratio (OR): 2.149, P = 0.039) was independently related to improved pCR rate as validated by multivariate logistic regression, while it did not correlate with DFS or OS (both P &gt; 0.05) by univariate and multivariate Cox’s regression analyses. Moreover, female gender ( P=0.001) and radiation dose ≥40 Gy. ( P = 0.039) could independently predict better pCR rate; and pCR rate was independently related to longer DFS ( P = 0.003) and OS ( P = 0.008). Conclusions: The prolonged time interval from nCRT to surgery relates to a higher pCR rate but does not correlate with DFS or OS in ESC patients.